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41.
Nahuel A. Ramella Isabel Andújar José L. Ríos Silvana A. Rosú M. Alejandra Tricerri Guillermo R. Schinella 《Pathophysiology》2018,25(4):397-404
The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation. 相似文献
42.
Paolo Borrione Chiara Fossati Maria Teresa Pereira Silvana Giannini Marco Davico Carlo Minganti 《Platelets》2018,29(6):596-601
The aim of the present retrospective observational study was to evaluate the time of functional recovery following a specific combined therapeutic approach characterized by an active exercise therapy carried out immediately after Platelet-rich plasma (PRP) injections for the treatment of the muscular lesion of the distal musculotendinous junction of the gastrocnemius medial head.Medical records of 31 subjects treated with three PRP intra-lesional ultrasound guided injections and 30 patients treated with the standard therapeutic approach (control group) were analyzed. Both groups followed the same rehabilitation therapy. Patients in the control group were able to start active exercise with a significant delay when compared to the PRP treated subjects: 17 ± 7.2 days and 9 ± 3.8 days (p = 0.0001), respectively. This delay was mainly due to the persistence of pain in the subjects in the control group. The time necessary to return to walk without pain was significantly shorter in the PRP treated group: 24.27 ± 12.36 days versus 52.4 ± 20.03 days in the control group (p < 0.001) as well as the time needed to fully return to practice the previous sport activity: 53.33 ± 27.74 days versus 119.3 ± 43.87 days in the control group (p < 0.001).The present study showed that ultrasound guided delivery of PRP into the site of muscle injury has to be considered a valid therapeutic approach with the potentiality of significantly reduce time and costs for reaching a complete functional recovery. 相似文献
43.
Mario Salmeri Carla Motta Silvana Mastrojeni Andrea Amodeo Carmelina Daniela Anfuso Giovanni Giurdanella Angela Morello Mario Alberghina Maria Antonietta Toscano Gabriella Lupo 《Neuroscience letters》2012
Escherichia coli K1 is the most common Gram-negative organism that causes neonatal meningitis following penetration of the blood–brain barrier. In the present study we demonstrated the involvement of cytosolic (cPLA2) and calcium-independent phospholipase A2 (iPLA2) and the contribution of cyclooxygenase-2 products in E. coli invasion of microvascular endothelial cells. The traversal of bacteria did not determine trans-endothelial electrical resistance (TEER) and ZO-1 expression changes and was reduced by PLA2s siRNA. cPLA2 and iPLA2 enzyme activities and cPLA2 phosphorylation were stimulated after E. coli incubation and were attenuated by PLA2, PI3-K, ERK 1/2 inhibitors. Our results demonstrate the role of PKCα/ERK/MAPK signaling pathways in governing the E. coli penetration into the brain. 相似文献
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45.
Daniela Delwing-de Lima Ariene Sampaio Souza Farias Ulbricht Carla Werlang-Coelho Débora Delwing-Dal Magro Victor Hugo Antonio Joaquim Eloise Mariani Salamaia Silvana Rodrigues de Quevedo Larissa Desordi 《The journal of physiological sciences : JPS》2018,68(5):699-706
We evaluated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) protocols on the alterations in oxidative stress parameters caused by a high-fat diet (HFD), in the blood and liver of rats. The HFD enhanced thiobarbituric acid reactive substances (TBA-RS) and protein carbonyl content, while reducing total sulfhydryl content and catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the blood. Both training protocols prevented an increase in TBA-RS and protein carbonyl content, and prevented a reduction in CAT. HIIT protocol enhanced SOD activity. In the liver, HFD didn’t alter TBA-RS, total sulfhydryl content or SOD, but increased protein carbonyl content and CAT and decreased GSH-Px. The exercise protocols prevented the increase in protein carbonyl content and the MICT protocol prevented an alteration in CAT. In conclusion, HFD elicits oxidative stress in the blood and liver and both protocols prevented most of the alterations in the oxidative stress parameters. 相似文献
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47.
The purpose of this study was to conduct a needs assessment of a potential social service resource telephone program component among high risk youth who received the Project Towards No Drug Abuse (TND) classroom-based program (approximately 1 year earlier). Results supported youths' overwhelming receptiveness of a social service referral program. The vast majority of respondents indicated a strong desire for resource and referral information on vocational, educational, recreational, transportation, and mental health and drug counseling. Further research is needed to investigate the effectiveness of the provision of social service resource information on drug use among emerging adults. 相似文献
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49.
Puri V Ranjit S Konda S Nicoloro SM Straubhaar J Chawla A Chouinard M Lin C Burkart A Corvera S Perugini RA Czech MP 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(22):7833-7838
Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans. 相似文献
50.
Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene 总被引:7,自引:0,他引:7 下载免费PDF全文
Borrello MG Alberti L Fischer A Degl'innocenti D Ferrario C Gariboldi M Marchesi F Allavena P Greco A Collini P Pilotti S Cassinelli G Bressan P Fugazzola L Mantovani A Pierotti MA 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(41):14825-14830
Rearrangements of the RET receptor tyrosine kinase gene generating RET/PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET/PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of genes involved in inflammation and tumor invasion, including those encoding chemokines (CCL2, CCL20, CXCL8, and CXCL12), chemokine receptors (CXCR4), cytokines (IL1B, CSF-1, GM-CSF, and G-CSF), matrix-degrading enzymes (metalloproteases and urokinase-type plasminogen activator and its receptor), and adhesion molecules (L-selectin). This effect is strictly dependent on the presence of the RET/PTC1 Tyr-451 (corresponding to RET Tyr-1062 multidocking site). Selected relevant genes (CCL20, CCL2, CXCL8, CXCR4, L-selectin, GM-CSF, IL1B, MMP9, UPA, and SPP1/OPN) were found up-regulated also in clinical samples of PTC, particularly those characterized by RET/PTC activation, local extrathyroid spread, and lymph node metastases, when compared with normal thyroid tissue or follicular thyroid carcinoma. These results, demonstrating that the RET/PTC1 oncogene activates a proinflammatory program, provide a direct link between a transforming human oncogene, inflammation, and malignant behavior. 相似文献